Pilot study of combined FDG-PET and dynamic contrast-enhanced CT of locally advanced cervical carcinoma before and during concurrent chemoradiotherapy suggests association between changes in tumor blood volume and treatment response

Abstract

Modern PET/CT radiotherapy simulators offer FDG-PET and dynamic contrast-enhanced (DCE) CT imaging for combined volumetric assessment of tumor metabolism and perfusion. However, the clinical utility of such assessment has not been clearly defined. Thus, in a prospective longitudinal study of primary cervical tumors treated with concurrent chemoradiotherapy (CCRT) we evaluated: (1) whether PET and perfusion parameters correlate or provide complementary information; (2) what imaging changes occur during CCRT; and (3) whether any parameters are predictive of treatment response as assessed by PET/CT 3 months posttherapy. FDG-PET/CT and DCE-CT scans were performed on 21 patients prior to and during CCRT. Coregistered volumetric parametric maps of standardized uptake value (SUV) measures and perfusion parameters blood flow (BF), blood volume (BV), and permeability were generated. Summary statistics for these parameters and their changes were calculated within the metabolic tumor volume (MTV). Correlations between SUV and BF/BV/permeability on local and global bases were assessed with Pearson's coefficient r. MTV, maximum SUV, and mean SUV decreased significantly between the pre- and during-treatment time points, while mean BV and permeability increased significantly. Global correlations between mean BF/BV/permeability and mean SUV values (-.15 < r < .29) were at most moderate. An increase in mean tumor BV during treatment was significantly correlated with complete metabolic response on 3-month posttreatment PET/CT. Weak correlations of SUV and perfusion parameters suggest a complementary role of FDG-PET and DCE-CT for tumor characterization. The association between relative change in mean BV and outcome suggests a potential role for DCE-CT in early evaluation of cervical tumor response to chemoradiotherapy.

Keywords: DCE-CT; FDG-PET; blood flow; blood volume; cervical cancer; cervix cancer; perfusion; permeability; radiotherapy.

Figure 1

Axial and coronal slices from pre‐ and during‐treatment volumetric maps of standardized uptake value (SUV), blood flow (BF), and blood volume (BV) for 2 patients. The patient shown in (A) and (B) exhibited complete metabolic response at initial posttreatment follow‐up, while the patient shown in (C) and (D) exhibited new distant disease at their same follow‐up

Figure 2

Bivariate scatterplots of global tumor standardized uptake value (SUV) and perfusion parameters extracted from pretreatment scans, as well as the patient distribution for each parameter. (See text for parameter definitions.) In each scatterplot, the sample correlation coefficient (r value) and 95%‐level confidence regions are shown. Moderate correlations are evident within the separate SUV and perfusion parameter groups but there is no indication of correlations between SUV and perfusion parameters. The during‐treatment data exhibit similar behavior

Figure 3

Changes in standardized uptake value (SUV) and perfusion parameters between pre‐ and during‐treatment scans for the analyzed patients. In each plot, the significance of a nonzero average change in parameter value during this early treatment period is indicated by the P‐value, which is based on a paired t test analysis in which the normality assumption was verified via residual analysis. The lines are colored according to individual patient outcome

Figure 4

Waterfall plot of relative mean blood volume (BV) changes between pre‐ and during‐treatment DCE‐CT scans for the patients studied. (Inset) Firth's bias‐adjusted logistic regression model with confidence limits for the probability of complete metabolic response (CMR) as a function of mean BV relative change (P = .0007)